6TDE
Tubulin-inhibitor complex
Summary for 6TDE
| Entry DOI | 10.2210/pdb6tde/pdb |
| Descriptor | Tubulin alpha chain, Tubulin beta chain, Stathmin-4, ... (9 entities in total) |
| Functional Keywords | cytoskeleton, cell division, intracellular transport, cell cycle |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 5 |
| Total formula weight | 220791.47 |
| Authors | Varela, P.F.,Gigant, B. (deposition date: 2019-11-08, release date: 2020-09-02, Last modification date: 2024-11-20) |
| Primary citation | Shchegravina, E.S.,Svirshchevskaya, E.V.,Combes, S.,Allegro, D.,Barbier, P.,Gigant, B.,Varela, P.F.,Gavryushin, A.E.,Kobanova, D.A.,Shchekotikhin, A.E.,Fedorov, A.Y. Discovery of dihydrofuranoallocolchicinoids - Highly potent antimitotic agents with low acute toxicity. Eur.J.Med.Chem., 207:112724-112724, 2020 Cited by PubMed Abstract: Two series of heterocyclic colchicinoids bearing β-methylenedihydrofuran or 2H-pyran-2-one fragments were synthesized by the intramolecular Heck reaction. Methylenedihydrofuran compounds 9a and 9h were found to be the most cytotoxic among currently known colchicinoids, exhibiting outstanding antiproliferative activity on tumor cell lines in picomolar (0.01-2.1 nM) range of concentrations. Compound 9a potently and substoichiometrically inhibits microtubule formation in vitro, being an order of magnitude more active in this assay than colchicine. Derivatives 9a and 9h revealed relatively low acute toxicity in mice (LD ≥ 10 mg/kg i.v.). The X-Ray structure of colchicinoid 9a bound to tubulin confirmed interaction of this compound with the colchicine binding site of tubulin. PubMed: 32827941DOI: 10.1016/j.ejmech.2020.112724 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.286 Å) |
Structure validation
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